PROJECT SUMMARY The Older American Independence Center (OAIC) Metabolism and Biomarkers Core in collaboration with all other Cores, utilizes translational research to determine specific mechanisms of sarcopenia and the cause of reduced physical function in elderly populations. Sarcopenia is characterized by a progressive deterioration in various physiological and metabolic processes and is associated with lower physical function. Analyses performed by the Core focus on mitochondrial function, inflammation, oxidative stress, apoptosis and autophagy, biological factors implicated to cause aging. The Core supports the hypothesis that mitochondrial dysfunction, inflammation, oxidative stress and deregulation of apoptosis and autophagy are major causes of sarcopenia and disability. Supported research proposals will contain refined questions and utilize selected methodologies addressing potential causes of sarcopenia and altered physical function. Importantly, the Core is a central facility for acquiring research data and new laboratory skills. Training and instruction is provided either one on one or through organized workshops. By acquiring new laboratory skills and techniques Junior investigators and Pepper Scholars can further develop their research interests independently. In addition, the diversity of research experience and skills among personnel within the core as well as scientists utilizing its facilities provides a rich environment for scientific discussion and collaborations. The Core also provides consultations to scientists who are either interested in new areas of research or unfamiliar with certain techniques. Thus, this Core provides the infrastructure and training necessary to develop our understanding of the mechanisms contributing to the aging process. Furthermore, we are committed to fostering novel technologies in our pursuit of deciphering the central role that mitochondrial dysfunction plays in the pathogenesis of diseases and aging. To this end we have recently developed innovative intravital-multiphoton excitation laser-scanning microscopy and high-resolution respirometry techniques to assess mitochondrial function in intact freshly isolated small (20-40 mg) muscle samples. Thus, we are now able to determine mitochondrial function in-situ, which is more reflective of the natural state. Other areas of focus include inflammation, oxidative stress (including iron deposition), apoptosis and autophagy biomarkers. In summary, by measuring a small selected set of cellular and molecular markers in skeletal muscle tissue we can assess a unique and comprehensive spectrum of age-related alterations with the goal of determining the mechanisms contributing to sarcopenia.